It is known that phytophagous mites are potentially the most important pests damaging the cultivated food-industrial and ornamental plants as well as stored crops whereas ectoparasitic mites are severely dangerous from the viewpoint of public and veterinary hygiene. The loss caused by phytophagous mites has mounted quickly and the importance of protection from them has abruptly increased. This can essentially be attributed to two reasons:
1) The predators and parasites maintaining the mite populations below the threshold value of loss were thinned by the use of nonselective insecticides. PA0 2) Due to the high number of generations and adaptability, a resistance of mites has developed within a relatively short period. PA0 1) Their higher efficiency provides a lower specific dose and decreased load on the environment. PA0 2) Due to their excellent translaminar activity, the mite eggs avoiding the spraying are also killed. PA0 3) Due to their excellent transovarian effect, sterile eggs develop in the feeding females. PA0 4) Their systemic action results in a significant broadening of the spectrum of effects and consequently of the scope of their employment. PA0 5) Due to their longer duration of effect and transovarian activity, the times of optimum protection can be determined more easily from a technological point of view. PA0 6) Due to their transovarian effect, they are useful for developing environment-sparing processes of plant protection (e.g. protection after harvesting). PA0 a) reacting a substituted bis-azine of formula (II) ##STR4## wherein X and Y are as defined above, and A as well as B stand for cleavable groups, with hydrazine of formula (III), EQU H.sub.2 N-NH.sub.2 (III) PA0 c) oxidizing a 3,6-disubstituted-1,2-dihydro-1,2,4,5-tetrazine derivative of the formula (IV), wherein X and Y are as defined above.
Typical representatives of harmful mite species in question are: spider mite (Tetranychus urticae), itch-mite (Psoroptes cuniculi), red spider mite (Tetranychus cinnabarinus) and other species hereinafter listed in detail.
Due to the increasing loss caused by mites, the development of highly effective, specific acaricides came into the limelight. For this purpose, a high number of tetrazine derivatives have been synthesized by various research groups (see the published European patent applications Nos. 5912, 29657 and 248,466 as well as the Hungarian patent specification No. 184,684).
In the published European patent application no. 5912 several 3,6-bis(2-halophenyl)-1,2,4,5-tetrazines and 3,6-bis(2-halophenyl)-1,2,-dihydro-1,2,4,5-tetrazines are disclosed, wherein the halogens, being the same or different for each compound, may be fluorine, chlorine or bromine. In the published European patent application No. 29657 a number of other 3,6-bis(2-halophenyl)-1,2,4,5-tetrazines, too, are described. From these compounds 3,6-bis(2-chlorophenyl)-1,2,4,5-tetrazine described in the published European patent application no. 5912 became commercially available under the trade name Apollo.RTM. (clofentezine; Pesticide Manual 1987, page 188). Being inactive against adult individuals and nymphs as development stages of mites, clofentezine is a selectively ovicidal compound. Among its advantageous properties, it is worth mentioning that it is selective (due to its novel mechanism of action), highly active, nontoxic to warm-blooded species, has a prolonged action and is essentially safe for useful living organisms [Entomophaga 36, pages 55-67 (1991)].
However, despite many advantages of clofentezine, it is also known that it has a contact effect, is not absorbed through the leaf and consequently, it is ineffective against the unsprayed mite eggs being present e.g. on the abaxial surface of the leaf [Pestic. Sci. 18, pages 179-190 (1987)].
The complete coverage of the foliage is not assured practically in any case. Thus, compositions which can penetrate into the plant and be then translocated to the proper site, are only effective against pests living in a hidden manner of life or residing in a resting immobile state at a safe site.
Based on the above knowledge, the aim of this invention is to develop an ovicidally active acaricide which, while possessing the favorable properties of clofetezine, exerts an additional excellent translaminer effect.
Thus, a high number of new tetrazine derivatives not described up to the present have been synthesized and the influence of modifications of the molecular structure on the translaminar acaricidal effect, especially the ovicidal effect was studied.
It has been found that 3,6-diphenyl-1,2,4,5-tetrazine derivatives of the formula (I), ##STR2## wherein
X means fluorine, chlorine or bromine; and
Y stands for fluorine or hydrogen,
substituted by fluorine, chlorine or bromine in the ortho-position and containing fluorine or hydrogen in the ortho'-position of the 3-phenyl group as well as substituted by fluorine both in the ortho- and ortho'-positions of the 6-phenyl group, possess an essentially new property, i.e. translaminar activity in addition to their stronger, inherent ovicidal effect. This bears a decisive importance for their practical utilization. Preferred representatives of the compounds of formula (I) are 3-(2-bromophenyl)-6-(2,6-difluorophenyl)-1,2,4,5-tetrazine, 3,6-bis(2,6-di fluorophenyl)-1,2,4,5-tetrazine and 3-(2-chlorophenyl)-6-(2,6-difluorophenyl)-1,2,4,5-tetrazine as well as their tautomers.
In addition, the compounds of formula (I) according to the invention exert also a systemic effect namely, they act after being absorbed through the root and translocated into the sprout.
The advantages of the compound of the formula (I) of the present invention may be summarized as follows (but without any limitation thereto).
The compounds of formula (I) or the compositions containing them, respectively give excellent results against Tetranychus urticae, Tetranychus cinnabarinus, Tetranychus viennensis, Panonychus ulmi, Bryobia and Schizotetranychus species belonging to the Tetranychus family; as well as against many species belonging to the Eriophydae and Tenuipalpidae families; furthermore, they can be employed with good results in all areas endangered by a loss caused by mites, e.g. in the protection of stores or in public and veterinary hygiene. In the latter uses, the more important pests are exemplified by the Boophilus, Dermacentor, Ixodes, Rhipicephalus, Psoroptes and Sarcoptes species.
The compounds of formula (I) according to the invention can be transformed to compositions by using processes commonly known for plant-protective, pesticidal and veterinary hygienic formulations which can equally be applied onto plants, stored crops, soil and farm animals.
These compounds are soluble e.g. in water-immiscible solvents such as high-boiling hydrocarbons (e.g. xylene) as vehicles containing suitable emulsifying agents; thus, after being added to water, these compositions behave as self-emulsifying oils.
Alternatively, the substituted tetrazines may be mixed with a wetting agent and optionally with a solid carrier to obtain wettable powders that are soluble or dispersible in water or mixed with solid carriers, too, to prepare solid products.
An aqueous suspension concentrate may also be prepared by grinding the active ingredient together with water, wetting and suspending agent.
The surfactant may be non-ionic, anionic or cationic in its character.
Preferable surfactants are e.g. ethoxylated fatty alcohol sulfates, ligninsulfonates, alkylaryl sulfonates, salts of sulfonated naphthalene/formaldehyde condensates, salts of sulfonated phenol/formaldehyde condensates, sodium oleyl-N-methyltauride, dialkyl sulfosuccinates, alkylphenyl ethoxylates and fatty alkyl ethoxylates.
In addition to the substituted tetrazines, the compositions of the invention may contain also other active ingredients, e.g. insecticidal, acaricidal, ovicidal, bactericidal or fungtcidal agents.
The compositions containing the active ingredients of formula (I) may be used at any site infested by mites or where the eggs or larvae of mites are present or expected to occur. The compositions according to the invention may be used e.g. on plants, animals or the soil.
Plants which can be treated with the compositions according to the invention are e.g.: sorts of cereals, plantation and ornamental plants such as cotton, tobacco, rice, fruit-trees and cereals, e.g. apple-tree, pear-tree, apricot-tree, peach-tree, citrus sorts, maize, barley or wheat, bean, sugar-beet, potato or carrot; or greenhouse plants and crops, e.g. pepper, tomato, cucumber, melon and strawberry.
For the various uses, the compositions containing the compounds of formula (I) may be employed in various amounts. Thus, 17 to 1120 g/hectare (g/ha) amounts of a composition may be applied onto the plant; or concentrations of 1 to 2000 ppm, preferably 100 to 11000 ppm, especially 35 to 280 g/ha of active agent may be used for killing the pests damaging the plants.
The novel compounds of formula (I) according to the invention can be prepared according to methods known in the art as described in detail in the published European patent application No. 59112.
Thus, the compounds of formula (I) ##STR3## wherein
X means fluorine, chlorine or bromine; and
Y stands for fluorine or hydrogen,
are prepared by
or the hydrate thereof, then oxidizing the obtained 3,6-disubstituted-1,2-dihydro-1,2,4,5-tetrazine of formula (IV), ##STR5## wherein X and Y are as defined above; or b) reacting a 1,3,4-thiadiazole derivative of formula ##STR6## wherein X and Y are as defined above, with an alkyl sulfate of formula (VII) EQU R.sub.2 SO.sub.4 (VII)
wherein R represents a C.sub.1-4 alkyl group, then transforming the obtained thiadiazolium salt of formula (VI), ##STR7## wherein X, Y, and R are as defined above, with hydrazine of the formula (III) or the hydrate thereof, and subsequently oxidizing the resulting 3,6-disubstituted-1,2-dihydro-1,2,4,5-tetrazine of formula (IV), wherein X and Y are as defined above; or
The preparation of the starting compounds of formula (II) and (V) from commercially available products is described in the published European patent application No. 5912.
The invention also relates to the 1,2-dihydro-1,2,4,5-tetrazines of the Formula (IV) ##STR8## These compounds are not only intermediates used in the preparation of the compounds of the Formula (I) having acaricidal, larvicidal, and ovicidal activity, but furthermore the compounds of the Formula (IV) themselves possess per se acaricidal, larvicidal, and ovicidal activity. These compounds can be applied in the same fashion as disclosed for the compounds of the Formula (I) to exert an acaricidal, larvicidal and ovicidal effect.
Preferred species of the Formula (IV) include the following:
3-(2-chlorophenyl)-6-(2,6-difluorophenyl)-1,2-dihydro-1,2,4,5-tetrazine;
3-(2-bromophenyl)-6-(2,6-difluorophenyl)-1,2-dihydro-1,2,4,5-tetrazine; and
3,6-bis(2,6-difluorophenyl)-1,2-dihydro-1,2,4,5-tetrazine.
The synthesis of the compounds of formula (I) and formula (IV) as well as substances disclosed in the published European paten application No. 5912 used as reference substances is illustrated in detail in the following non-limiting examples.
Further examples show the preparation of compositions from compounds of the formula (I). The biological activity of compounds of formula (I) and formula (IV) according to the invention is demonstrated in the Biological Examples.
The examples are only illustrative without any limitation thereto.